Brainstem Concentrations of Cholesterol are not Influenced by Genetic Ablation of the Low-Density Lipoprotein Receptor

Purpose The low-density lipoprotein receptor (LDLr) mediates the uptake of LDL particles enriched with cholesterol, into several tissues. In contrast to other tissues, the brain is thought to obtain cholesterol solely by de novo synthesis, yet certain brain regions such as the brainstem are highly enriched with the LDLr. The goal of the present study was to assess the role of the LDLr in maintaining cholesterol concentrations in the brainstem of wildtype and LDLr knockout (LDLr-/-) mice. Cholesterol concentrations were also measured in the cortex, which served as a reference point, due to the lower expression of the LDLr, as compared to the brainstem. Methods LDLr-/- and wildtype mice consumed an AIN-93G diet ad libitum until 7 weeks of age. After microwaving, the cortex and anterior brain stem were isolated for cholesterol analysis. Cholesterol was extracted into chloroform/methanol, derivatized in trimethylsilyl chloride and measured by gas chromatography/mass spectrometry. Results Concentrations of cholesterol in the brainstem did not differ statistically between LDLr-/- (18.8 +/- A 1.6 mg/g wet weight brain) and wildtype (19.1 +/- A 2.0). Cortical cholesterol concentrations also did not differ statistically between LDLr-/- (11.0 +/- A 0.4 mg/g wet weight brain) and wildtype (11.1 +/- A 0.2) mice. Conclusion The LDLr is not necessary for maintaining cholesterol concentrations in the cortex or brainstem, suggesting that other mechanisms are sufficient to maintain brain cholesterol concentrations.